Method for preparing polyazacycloalkanes grafted on silica gel and use of grafted compounds

ABSTRACT

The invention concerns a method for preparing polyazacycloalkanes immobilised on a silica gel from a polyazacycloalkane of formula (A) in which: R 1  and R 2  represent a hydrogen atom, an alkyl radical, or a [hetero(aryl)]alkyl radical; W 1 , W 2  and W 3  represent a radical of formula (B): —[(CT 1 T 2 ) n —[N(R 3 )] p —(CT 3 T 4 ) m ] l — such as defined in the description; R 3  represents a hydrogen atom, an alkyl radical or a [hetero(aryl)]alkyl radical, provided that the polyazacycloalkane ring of the compound of formula (A) comprises not more than 30 cyclic carbon atoms, and not more than 6 cyclic nitrogen atoms. The invention is characterised in that: (a) the compound of formula (A) is reacted with a compound of formula (C): Z—R 4 —Si(X 1 )(X 2 )(X 3 ), such as defined in the description to form a compound of formula (D); (b) said compound of formula (D) is condensed on the silanol sites of a silica gel to form the immobilised polyazacycloalkane of formula (E); and (c) some ethanol sites having not reacted are, if required, protected by Z′, a group protecting the hydroxyl function. The invention is useful for separating oxygen from air.

Polyazamacrocyclic compounds are of considerable interest in the fieldof coordination chemistry. These ligands in particular form stablecomplexes with transition elements and heavy metals (Bradshaw J. S,Krakowiak K. E, Izatt R. M, Aza-crown Macrocycles in The Chemistry ofHeterocyclic Compounds; edited by Taylor E. C, John Wiley & Son Inc.:New York, 1993, pp. 1-885; Izatt R. M, Pawlak K, Bradshaw J. S, BrueningR. L, Chem. Rev., 1995, 95, 2529-2586). The dimensions of themacrocyclic cavity, the shape and the rigidity of the ring, the size ofthe chelated ring, and the number and the nature of the substituentscarried by the nitrogen atoms are all factors which influence theaffinity of the ligand with respect to a given metal ion and thus theselectivity with respect to other elements. These properties have madepossible the use of these compounds in fields as varied as the selectivecoordination of atmospheric dioxygen (Cabani S. React. and Funct.Polym., 1996, 167-182; Machida R, Kimura E, Kodama M, Inorg. Chem.,1983, 22, 2055-2061), medical imaging (Alexander V, Chem. Rev., 1995,95, 273-342) or the extraction of metal elements (Guilard, R, Chollet H,Guiberteau P, Cocolios P, WO 96/11189, published on Apr. 18, 1996, FR2725382 published on Apr. 12, 1996; Izatt R. M, Bruening R. L, Borup M.B, Water Sci. Technol., 1991, 23, 301-308).

In the field of the extraction of heavy metals and of the purificationof effluents, the major disadvantage of these nitrogenous macrocycles istheir solubility both in water and organic solvents, which results in aloss of the ligand when it is used in a liquid—liquid extractionprocess. On the other hand, the immobilization of the ligand on a solidsupport makes possible the development of a solid-liquid extractionprocess which exhibits numerous advantages, such as a reduced cost (noloss of the ligand), the noncontamination of the solvents to bepurified, and easy use and regeneration of the columns. In the contextof gas separation or purification, it is known, for example, thattetraazamacrocyclic cobalt complexes exhibit a high affinity withrespect to dioxygen. However, the superoxide oxygen-comprising speciesformed can change in the direction of species of μ-peroxo type whichhave a limited lifetime in solution, where they undergo irreversibledecomposition reactions (Martell A. E, Basak A. K, Raleigh C. J, PureAppl. Chem., 1988, 60, 1325-1329). The attachment of the active complexto a solid matrix results in the superoxide species, which promotes thereversibility of the reaction and limits the decomposition of theoxygen-comprising species. Thus, absorption/desorption cycles might becarried out by lowering the pressure and/or raising the temperature.

Some industrial sectors, for example electronics, use liquids or gasesof very high purity and environmental standards are becomingincreasingly strict. Consequently, the development of processes whichmake it possible to remove trace amounts constitutes a priority. To thisend, numerous modified polymers possessing selective chelatingproperties have been developed. Silica gels are among the most widelyused supports (Biernat J. F, Konieczka P, Tarbet B. J, Bradshaw J. S,Izatt R. M, Sep. Purif. Methods, 1994, 23, 77-348). This is because theyexhibit numerous advantages with respect to organic polymers: they areinexpensive, mechanically and thermally stable, inert with respect tonumerous chemicals and insoluble in most organic solvents and can beeasily modified.

Various silica gels modified by polyazamacrocyclic ligands have alreadybeen synthesized (Gros C, Rabiet F, Denat F, Brandes S, Chollet H,Guilard R, J. Chem. Soc. Dalton Trans., 1996, 1209-1214; Subba Rao Y. V,De Vos D. E, Bein T, Jacobs P. A, Chem. Commun., 1997, 355-356; BagnoudM. A, Haerdi W, Veuthey J. L, Chromatographia, 1990, 29, 495-499; IzattR. M, Bruenig R. L, Tarbet B. J, Griffin L. D, Bruening M. L, KrakowiakK. E, Bradshaw J. S, Pure Appl. Chem., 1990, 62, 1115-1118; Dudler V,Lindoy L. F, Sallin D, Schlaepfer C. W, Aust. J Chem., 1987, 40,1557-1563). The most commonly used synthetic route (route A) isrepresented diagrammatically as follows:

During a first stage, a spacer arm carrying an electrophilic ending isattached to the silica gel by reaction of the appropriate silylatedreactant (generally an alkoxysilane) with the silanol sites. Variousassembling groups, such as those which appear hereinabove, can thus beused. The unreacted silanol sites can optionally be protected by theaction of trimethylchlorosilane, in order to increase the selectivity ofthe gel or the hydrophobic nature of the latter. The desired macrocycleis subsequently condensed onto the modified silica gel. In a finalstage, the grafted macrocycle can be N-substituted by the action of anappropriate electrophilic reactant. The amount of macrocycle graftedaccording to this synthetic scheme is approximately 0.35-0.40 mmol/g ofmaterial.

Another possible route of access to modified silica gels of this type(route B) consists, in a first stage, in functionalizing the macrocyclewith the spacer arm, the grafting onto the silica subsequently takingplace in a final stage: Bradshaw et al. (Izatt R. M, Bruening R. L,Tarbet B. J, Griffin L. D, Bruening M. L, Krakowiak K. E, Bradshaw J. S,Pure Appl. Chem., 1990, 62, 1115-1118, Bradshaw J. S, Krakowiak K. E,Tarbet B. J, Bruening R. L, Griffin L. D, Cash D. E, Rasmussen T. D,Izatt R. M, Solv. Extract Ion Exch., 1989, 7, 855-864) have thusdeveloped a method which makes it possible to graft pentaazamacrocyclesand various mixed (oxygen-nitrogen) macrocycles onto a silica gel,represented diagrammatically as follows:

In a first stage, a substituent carrying a terminal ethylene unit isattached to the desired macrocycle. The compound is subsequentlyhydrosilylated and the product thus obtained is condensed onto thesilica gel.

However, the first synthetic route (A) exhibits two major disadvantages:

Only 30 to 50% of the spacer arms grafted in the first stage react withthe macrocycle. The amount of grafted macrocycles is thus greatlyreduced thereby and the residual presence of the unreacted functionalgroups can prove to be harmful during the implementation of a processusing these materials for a given application.

The N-functionalization of the grafted tetraazamacrocycle, the finalstage in the synthesis, is not quantitative as only one to two secondaryamine functional groups of the three available react with theelectrophilic reactant. In addition, some macrocycles may be bonded bytwo nitrogen atoms to the silica gel. This heterogeneity is harmful tothe effectiveness and to the selectivity of the modified silica gel.

The synthetic route (B), while it makes it possible to control thesubstitution of the grafted ligand, is problematic to carry out,however, and it requires the use of expensive catalysts, such ashexachloroplatinic acid. The subject-matter of the present inventionprovides an unexpected solution to the problems set out hereinabove.

A subject-matter of the invention is a process for the preparation of apolyazacycloalkane, immobilized on a silica gel, from apolyazacycloalkane of formula (A):

in which

R₁ and R₂, which are identical or different, each represent,independently of one another, a hydrogen atom, a linear or branchedalkyl radical comprising from 1 to 15 carbon atoms,

W₁, W₂ and W₃, which are identical or different, represent,independently of one another, a divalent radical chosen from thoserepresented by the general formula (B):

—[(CT₁T₂)_(n)—[N(R₃)]_(p)—(CT₃T₄)_(m)]₁—  (B)

in which

p represents an integer equal to 1 or equal to 0,

l represents an integer equal to 1 or to 2,

n and m, which are identical or different, each represent, independentlyof one another, an integer less than or equal to 3 and greater than orequal to 1,

T₁, T₂, T₃ and T₄, which are identical or different, either eachrepresent, independently of one another, a hydrogen atom, a linear orbranched alkyl radical comprising from 1 to 15 carbon atoms or elseCT1T2 and/or CT3T4 represent the divalent group —(C═O)—,

R3 represents, independently of R1 or R2, a hydrogen atom, a liner orbranched alkyl radical comprising from 1 to 15 carbon atoms,

 which comprises:

a) the reaction of the compound of formula (A) with a compound offormula (C)

Z—R₄—Si(X₁)(X₂)(X₃)  (C)

 in which:

X₁, X₂ and X₃, which are identical or different, each represent,independently of one another, a hydrogen atom, a halogen atom or an OR₅radical, in which R₅ represents a hydrogen atom or an alkyl radicalcomprising from 1 to 4 carbon atoms,

R₄ represents a divalent radical derived from a saturated or unsaturatedaliphatic hydrocarbonaceous chain comprising from 1 to 10 carbon atoms,in which chain are optionally inserted one or more structural linkschosen from the arylene group or the —O—, —S—, —O—C(═O)—, —N(R₆)—C(═O)—or —N(R₆)— fragments, in which fragments R₆ represents a hydrogen atom,an aliphatic hydrocarbonaceous radical comprising from 1 to 6 carbonatoms, a benzyl radical or a phenethyl radical, the said chain beingunsubstituted or substituted by one or more radicals chosen from halogenatoms, the hydroxyl group, alkyl radicals comprising from 1 to 4 carbonatoms or the benzyl or phenethyl radicals, and

Z represents a functional group capable of reacting with the secondaryamine functional group, ═N—H, to form an N—C covalent bond, to form acompound of formula (D),

 in which R′₄ represents either R₄ as defined above, or R₄ substitutedby a radical originating from the reaction of Z with the secondary aminegroup ═N—H,

b) the condensation of said compound of formula (D) with silanol sitesof a silica gel, to form the immobilized polyazacycloalkane of formula(E):

 in which:

X′₂ represents X₂ as defined above or O-(silica gel), and

X′₃ represents X₃ as defined above or O-(silica gel);

c) and the protection, if desired, of all or a portion of the freeunreacted silanol sites with Z′, a protective group for the hydroxylfunctional group.

The term “polyazacycloalkane of formula (A)” denotes non-immobilizedpolyazacycloalkanes known to a person skilled in the art at the date offiling of the present patent application.

When the compound of formula (A) comprises three cyclic nitrogen atoms,it is in particular 1,4,7-triazacyclononane, 1,4,7-triazacyclodecane or1,4,8-triazacyclododecane.

When the compound of formula (A) comprises four cyclic nitrogen atoms,it is in particular 1,4,7,10-tetraazacyclododecane (cyclene),1,4,7,10-tetraaza-cyclotridecane, 1,4,7,11-tetraazacyclotetradecane,1,4,8,11-tetraazacyclotetradecane (cyclam),1,4,8,12-tetraazacyclopentadecane, 1,5,9,13-tetraazacyclohexa-decane or1,5,10,14-tetraazacyclooctadecane.

When the compound of formula (A) comprises five cyclic nitrogen atoms,it is in particular 1,4,7,10,13-pentaazacyclopentadecane,1,4,7,11,15-pentaazacyclo-octadecane or1,5,9,13,17-pentaazacyclooctadecane.

When the compound of formula (A) comprises six cyclic nitrogen atoms, itis in particular 1,4,7,10,13,16-hexaazacyclooctadecane or1,5,9,13,17,20-hexaazacyclotetracosane.

The compound of formula (A) can be unsubstituted or substituted; when itis substituted, the substituents are chosen from those which do notreact under the operating conditions with the compound of formula (B);examples of substituted polyazacycloalkanes are those substituted byalkyl radicals comprising from 1 to 15 carbon atoms or the benzyl,picolyl or phenethyl radicals, such as6-dodecyl-1,4,8,11-tetraazacyclotetradecane,3-dodecyl-1,5,9,13-tetraazacyclohexadecane,3-dodecyl-1,5,10,14-tetraazacyclooctadecane,5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane,1,4,7,10,13-pentaethyl-1,4,7,10,13,16-hexaazacyclooctadecane,1,7,10-tetraethyl-1,4,7,10,13-pentaazacyclopentadecane,1-methyl-1,4,8,11-tetraazacyclotetradecane,1-benzyl-1,4,8,11-tetraazacyclotetradecane,1-[(2-pyridyl)-methyl]-1,4,8,11-tetraazacyclotetradecane,1-[(3-pyridyl)methyl]-1,4,8,11-tetraazacyclotetradecane or1,4-dibenzyl-1,4,8,11-tetraazacyclotetradecane.

The term “functional group capable of reacting with a secondary amine”denotes in particular those which react according to a nucleophilicsubstitution mechanism, such as, for example, the halogen radicals andparticularly the iodo radical, or those which react according to anelectrophilic addition mechanism, such as, for example, the epoxyfunctional group, which results in an N—CH₂—CH(OH) fragment; it can alsobe a free, salified or esterified carboxyl functional group or a CH₂═CH—group, which results in an N—CH₂—CH₂— fragment via a reaction of“Michael” type according to a nucleophilic addition mechanism. Theseexamples do not have a limiting nature and it is obvious that anyfunctional group known to a person skilled in the art at the date offiling of the present patent application as being capable of reactingwith a secondary amine functional group to form an N—CH covalent bondforms an integral part of the present description of the invention.

The term “protective group for the hydroxyl functional group” denotes,for Z′, any group resulting from an etherification or esterificationreaction with Si—OH; mention may in particular be made, as example of Z′group, of the trialkylsilyl radical in which each of the alkyl radicalscomprises, independently of one another, from 1 to 4 carbon atoms.

According to a first specific aspect of the process as defined above,the latter is carried out with a compound of formula (C₁):

Z″—(CH₂)_(o)—(Q)_(q)—(CH₂)_(r)—(Ar)_(s)—(CH₂)_(t)—(U)_(u)—(CH₂)_(v)—Si(X₁)(X_(s))(X₃)  (C₁)

corresponding to the formula (C) in which Z—R₄ represents the radical:

Z″—(CH₂)_(o)—(Q)_(q)—(CH₂)_(r)—(Ar)_(s)—(CH₂)_(t)—(U)_(u)—(CH₂)_(v)—

in which:

Z″ represents either a halo radical or an R₇O—C(═O)— group, in which R₇represents a hydrogen atom, a sodium atom, a potassium atom or a radicalchosen from alkyl radicals comprising from 1 to 4 carbon atoms or thetosyl, mesyl or trifluoromethylsulfonyl radicals, or an oxiran-2-ylgroup or an ethenyl group,

o, r, t and v, which are identical or different, represent,independently of one another, an integer greater than or equal to 0 andless than or equal to 6,

Q and U, which are identical or different, represent, independently ofone another, an oxygen atom, a sulfur atom or one of the —O—CO—, —CO—O—,—NH—CO—, —CO—NH— or —NH— groups,

q, s and u, which are identical or different, represent, independentlyof one another, an integer greater than or equal to 0 and less than orequal to 1,

Ar represents an arylene radical and in particular a phenylene radical,

it being understood that:

when q is equal to 1, o is other than 0,

when q is equal to 1 and when u is equal to 0, the sum r+s+t+v is otherthan 0,

when u is equal to 1, v is other than 0,

when u is equal to 1 and when q is equal to 0, the sum o+r+s+t is otherthan 0,

when s is equal to 0 and when q and u are each equal to 1, the sum r+tis other than 0, and

the sum o+r+t+v is less than or equal to 12.

The process which is the subject-matter of the present invention iscarried out in particular with a compound of formula (C₂), correspondingto the formula (C₁) as defined above in which:

Z″ represents a bromo radical, an iodo radical or an oxiran-2-ylradical,

(X₁), (X₂) and (X₃) each represent an ethoxy radical or a methoxyradical,

the sum of o+r+t+v is less than or equal to 6 and

the sum of q+u is less than or equal to 1.

The process is carried out in particular with the following products:

(triethoxy)(3-iodopropyl)silane,

2-[[[3-(triethoxysilyl)propyl]oxy]methyl]-oxirane and

N-[[4-(bromomethyl)phenyl]methyl]-N-[3-(triethoxysilyl)propyllamine.

The compounds of formulae (C) and (C₁) are obtained from commerciallyavailable products by methods known to a person skilled in the art.

According to another specific aspect of the process as defined above,the latter is carried out from a compound of formula (A₁), correspondingto the formula (A) as defined above in which:

W₁, W₂ and W₃, which are identical or different, represent,independently of one another, a divalent radical chosen from thoserepresented by the general formula (B₁):

—(CH₂)_(n)—(NH)_(p)—(CH₂)_(m)—  (B₁)

 in which:

n and m are, independently of one another, equal to 2 or to 3 and p isequal to 0 or to 1.

The process is carried out in particular from a compound of formula(A₂), corresponding to the formula (A₁) in which the R₁ and R₂ radicalseach represent a hydrogen atom, and more particularly from cyclam, acompound of formula (A₂) as defined above in which W₁ represents thedivalent radical —(CH₂)₃—NH—(CH₂)₂—, W₂ represents the divalent radical—(CH₂)₂— and W₃ represents the divalent radical —(CH₂)₃—, or fromcyclene, a compound of formula (A₂) in which W₁ represents the divalentradical —(CH₂)₂—NH—(CH₂)₂— and W₂ and W₃ each represent the divalentradical —(CH₂)₂—.

In an alternative form of the process which is a subject-matter of thepresent invention, the compound of formula (D₁), corresponding to theformula (D) as defined above in which at least one of the R₁, R₂ or R₃radicals represents a hydrogen atom, is functionalized beforehand on oneor more of its cyclic nitrogens to form a compound of formula (D′)

in which:

R′₄, X₁, X₂ and X₃ are as defined above,

R′₁ and R′₂, which are identical or different, represent, independentlyof one another, a hydrogen atom, a linear or branched alkyl radicalcomprising from 1 to 15 carbon atoms, a [hetero(aryl)]alkyl radicalcomprising from 7 to 12 carbon atoms or a —(CH₂)_(w)—C(═O)—V radical inwhich V represents one of the OH, NH₂ or OR₈ radicals, in which R₈represents an alkyl radical comprising from 1 to 4 carbon atoms, and wrepresents an integer greater than or equal to 1 and less than or equalto 6;

W′₁, W′₂ and W′₃, which are identical or different, represent,independently of one another, a divalent radical chosen from thoserepresented by the general formula (B′):

—[(CT₁T₂)_(n)—[N(R′₃)]_(p)—(CT₃T₄)_(m)]_(l)—  (B′)

 in which:

p, l, n, m, T₁, T₂, T₃ and T₄ have the same meanings as those definedabove for the formula (B),

R′₃ represents, independently of R′1 or R′2, a hydrogen atom, a linearor branched alkyl radical comprising from 1 to 15 carbon atoms, or a

—(CH₂)_(w)—C(═O)—V radical in which V represents one of the OH, NH₂ orOR₈ radicals, in which R₈ represents an alkyl radical comprising from 1to 4 carbon atoms, and w represents an integer greater than or equal to1 and less than or equal to 6,

it being understood that at least one of the R′₁, R′₂ or R′₃ radicalsrepresents a —(CH₂)_(w)—C(═O)—V radical,

before being grafted onto the silanol sites of the silica gel to form animmobilized and functionalized macrocycle of formula (E′), correspondingto the formula (E) in which R₁, R₂ and R₃ represent R′₁, R′₂ and R′₃respectively.

When this alternative form of the process which is the subject-matter ofthe present invention is carried out, it is preferable to prepare acompound of formula (D′₁), corresponding to the formula (D′) as definedabove in which none of the R′₁, R′₂ or R′₃ radicals represents ahydrogen atom.

This alternative variant of the process is carried out in a particularlyappropriate way from the compound of formula (A₂) as defined above,which results in the compound of formula (D₂), corresponding to theformula (D) in which W₁, W₂, W₃, R₁ and R₂ are as defined in the formula(A₂), and then in the compound of formula (D′₂), corresponding to theformula (D′) as defined above in which R′₁, R′₂ and R′₃ each represent a—(CH₂)_(w′)—C(═O)—OR′₈ radical, in which w′ is equal to 1, 2 or 3 andR′₈ represents a hydrogen atom, a methyl radical or an ethyl radical.

The reactions for functionalizing the NH group are known to a personskilled in the art; one of them is disclosed in the international patentapplication published under No. WO96/11189 on Apr. 18, 1996.

Another subject-matter of the invention is the compounds of formulae (D)and (D′) as defined above, in particular the compounds of formulae (D₁),(D₂), (D′₁) and (D′₂) as defined above, and more particularly thefollowing products:

1-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclododecane,

1-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclotridecane,

1-[3-(triethoxysilyl)propyl]-1,4,8,11-tetraazacyclotetradecane,

1-[3-(triethoxysilyl)propyl]-1,4,8,12-tetraazacyclopentadecane,

1-[3-(triethoxysilyl)propyl]-1,5,9,13-tetraazacyclohexadecane,

1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,7,10-tetraazacyclododecane,

1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,7,10-tetraazacyclotridecane,

1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,8,11-tetraazacyclotetradecane,

1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,8,12-tetraazacyclopentadecane,

1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,5,9,13-tetraazacyclohexadecane,

1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,7,10-tetraazacyclododecane,

1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,7,10-tetraazacyclotridecane,

1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,8,11-tetraazacyclotetradecane,

1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,8,12-tetraazacyclopentadecane,

1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,5,9,13-tetraazacyclohexadecane,

ethyl10-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,

ethyl10-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,

ethyl11-[3-(triethoxysilyl)propyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,

ethyl12-[3-(triethoxysilyl)propyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,

ethyl13-[3-(triethoxysilyl)propyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate,

ethyl10-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,

ethyl10-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,

ethyl11-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,

ethyl12-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,

ethyl13-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate,

ethyl10-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,

ethyl10-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,

ethyl11-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,

ethyl12-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,and

ethyl13-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate.

An example of the implementation of the process according to theinvention is illustrated by the following schemes:

Iodopropyltriethoxysilane is synthesized simply by the action of NaI oncommercial chloropropyltriethoxysilane. The iodopropyltriethoxysilane,in solution in acetonitrile, is then added dropwise to a solution ofcyclam in acetonitrile at reflux in the presence of Na₂CO₃. The reactionmixture is maintained at reflux for 24 h, the solvent is subsequentlyevaporated and pentane is added to the residue. The excess insolublecyclam is filtered off, the filtrate is concentrated and compound 1 isobtained without subsequent purification with a yield of 50%. Thegrafting of 1 onto the silica gel is carried out at reflux of the xylenefor 4 days. The amount of grafted macrocycles is then 0.8 mmol/g ofmodified silica gel.

Compound 1 can be functionalized and then subsequently grafted accordingto the scheme:

Compound 1 is stirred for 4 days at room temperature in ethyl acrylate.After evaporating the ethyl acrylate and washing several times withpentane, the product 2 is obtained quantitatively. The grafting of 2onto the silica gel is subsequently carried out as described above.

If this methodology is compared with that which proceeds by grafting thespacer group onto the silica gel and then by attaching the desiredligand to this arm, this novel process makes it possible to double theamount of tetraazamacrocycles grafted at the surface of the silica gel.The number of “active sites” per unit of surface area is thussignificantly increased, resulting in a considerable improvement in theeffectiveness of the material. The second advantage, which is even moreimportant, is to be able to completely control the nature of the ligandattached, since it is synthesized, isolated and characterized beforegrafting.

This novel method for the synthesis of ligands carrying the spacer armdoes not require special experimental conditions and results, withsuitable yields, in the expected compounds without subsequentpurification. In addition, this synthesis is carried out in a singlestage and not two as in the methodology involving the hydrosilylation ofthe terminal alkene. Finally, the N-substitution of these novel ligandsis quantitative and makes possible the grafting of completelyN-substituted macrocycles.

This method applies not only to the compound of formula (A) as definedabove but also to linear polyamines. Various spacer arms (comprisingaromatic units or ester or amide functional groups) can be used. Theelectrophilic reactant used during the N-functionalization can alsovary, making possible access to a large range of silica gels exhibitingan optimum effectiveness and an optimum selectivity.

The macrocycles grafted onto a silica gel by the process which is thesubject-matter of the present invention are used for removing metalcations from a liquid, in particular removing cations chosen from U, Pu,Am, Ce, Eu, Al, Gd, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ag, Cd, Sn, Au, Hg orPb.

The macrocycles grafted onto a silica gel by the process which is thesubject-matter of the present invention are also used to preparecomplexes with transition metals, said transition metal complexes beingused for the separation and the removal of oxygen from a gas mixture,such as air, comprising it.

The following examples illustrate the invention without, however,limiting it.

Synthesis of (triethoxy)(3-iodopropyl)silane.

36.5 g (0.243 mol) of sodium iodide (dried at 100° C. under 1 mm Hg for24 h) are dissolved, under an argon atmosphere, in 150 ml of acetonewhich has been dried and distilled over a 4 Å molecular sieve. 58.6 g(0.243 mol) of chloropropyltriethoxysilane are then added dropwise andthe reaction mixture is brought to reflux for 24 h. The white sodiumchloride precipitate formed is then filtered off and the solvent isevaporated. The residue is distilled and the iodopropyltriethoxysilaneis obtained in the form of a slightly yellow liquid (46.6 g, 58%) (B.p.:120-125° C./1 mm Hg).

¹H NMR (δ ppm CDCl₃): 0.70 (m, 2H), 1.20 (t, 9H), 1.91 (m, 2H), 3.19 (t,2H), 3.80 (q, 6H). ¹³C NMR (δ ppm CDCl₃): 11.11, 13.14, 19.00, 28.42,59.21.

Synthesis of1-[3-(triethoxysilyl)propyl]-1,4,8,11-tetraazacyclotetradecane (compound1)

72 g (0.359 mol) of cyclam and 15 g of Na₂CO₃ (dried at 100° C. under 1mm Hg for 24 h) are placed in 2.5 l of acetonitrile in a 6 l reactorunder a stream of nitrogen. The mixture is brought to reflux, a solutionof 24.2 g (0.073 mol) of iodopropyltriethoxysilane in 500 ml ofacetonitrile is then added dropwise and then the reaction mixture ismaintained at reflux for 48 h. After evaporating the solvent on a rotaryevaporator (still under a nitrogen atmosphere), pentane is added to theresidue and the excess cyclam is filtered off. This operation isrepeated three times, the filtrates are combined, the pentane isevaporated and compound 1 is obtained in the form of a colorless oil (15g, 50.8%).

¹H NMR (δ ppm CDCl₃): 0.46 (m, 2H), 1.10 (t, 9H), 1.43 (m, 2H), 1.59 (m,4H), 2.30-2.70 (m, 18H), 3.69 (q, 6H). ¹³C NMR (δ ppm CDCl₃): 8.64,18.91, 26.92, 29.55, 48.35, 48.66, 49.60, 49.99, 50.08, 51.57, 53.92,55.17, 56.05, 58.88. Elemental analysis: for (C₁₉H₄₄N₄O₃Si); Calculated:C: 56.39%; H: 10.96%; N: 13.84%; Found: C: 56.13%; H: 11.01%; N: 12.76%.

Synthesis of ethyl11-[3-(triethoxysilyl)-propyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate(compound 2)

8.2 g (0.020 mol) of 1 and 70 ml of ethyl acrylate are stirred at roomtemperature for 4 days under an argon atmosphere. After evaporating theexcess ethyl acrylate and washing 3 times with pentane, compound 2 isobtained in the form of a yellow oil (14 g, 100%).

¹H NMR (δ ppm CDCl₃): 0.55 (m, 2H), 1.19 (t, 12H) , 1.23 (t, 12H) , 1.54(m, 6H) , 2.48 (m, 24H) , 2.71 (m, 6H), 3.78 (q, 6H), 4.09 (q, 6H). ¹³CNMR (δ ppm CDCl₃): 7.94, 14.21, 18.28, 20.46, 23.89, 31.03, 32.65, 50.63(broad), 51.18 (broad), 58.21, 60.14. Elemental analysis: for(C₃₄H₆₈N₄O₉Si): Calculated : C: 57.92%; H: 9.73%; N: 7.95%; Found : C:57.67%; H: 9.90%; N: 8.19%.

Grafting onto silica gel

The silica gel (Kieselgel 60, diameter 0.2-0.5 mm, specific surface 550m²/g, Merck) is dried beforehand by azeotropic distillation in xylene.The macrocycle and the silica gel (1.5 mmol per 1 g) are mixed andbrought to reflux of the xylene (10 ml per 1 g of silica) for 4 days.The silica gel is subsequently filtered off, washed successively withxylene, water, acetone and ethyl ether, and finally dried.

The percentage analysis of the nitrogen in the silica gels thus modifiedmakes it possible to determine the amount of grafted macrocycle:

for compound 1: 0.81 mmol per gram of material;

for compound 2: 0.60 mmol per gram of material.

The presence of the ester functional groups on the cyclam in compound 2results in a larger increase in mass, explaining the lower amount ofmacrocycle per gram of material.

What is claimed is:
 1. A process for the preparation of apolyazacycloalkane, immobilized on a silica gel, from apolyazacycloalkane of formula (A):

in which R₁ and R₂, which are identical or different, each represent,independently of one another, a hydrogen atom, a linear or branchedalkyl radical having from 1 to 15 carbon atoms, W₁, W₂ and W₃, which areidentical or different, represent, independently of one another, adivalent radical chosen from those represented by the general formula(B₁): —(CH₂)_(n)—(NH)_(p)—(CH₂)_(m)—  (B₁)  in which: n and m are,independently of one another, equal to 2 or to 3 and p is equal to 0 orto 1, it being understood that the polyazacycloalkane nucleus of thecompound of formula (A) has at most 30 cyclic carbon atoms and at most 6cyclic nitrogen atoms,  which comprises: a) the reaction of the compoundof formula (A) with a compound of formula (C₁)Z″—(CH₂)_(o)—(Q)_(q)—(CH₂)_(r)—(Ar)_(s)—(CH₂)_(t)—(U)_(u)—(CH₂)_(v)—Si(X₁)(X₂)(X₃)  (C₁) in which Z′ represents either a halo radical or an R₇O—C(═O)— group, inwhich R₇ represents a hydrogen atom, a sodium atom, a potassium atom ora radical chosen from alkyl radicals having from 1 to 4 carbon atoms orthe tosyl, mesyl or trifluoromethylsulfonyl radicals, or an oxiran-2-ylgroup or an ethenyl group, o, r, t and v, which are identical ordifferent, represent, independently of one another, an integer greaterthan or equal to 0 and less than or equal to 6, Q and U, which areidentical or different, represent, independently of one another, anoxygen atom, a sulfur atom or one of the —O—CO—, —CO—O—, —NH—CO—,—CO—NH— or —NH— groups, q, s and u, which are identical or different,represent, independently of one another, an integer greater than orequal to 0 and less than or equal to 1, Ar represents a phenyleneradical, it being understood that:  when q is equal to 1, o is otherthat 0,  when q is equal to 1 and when u is equal to 0, the sum r+s+t+vis other than 0,  when u is equal to 1, v is other than 0,  when u isequal to 1 and when q is equal to 0, the sum o+r+s+t is other than 0, when s is equal to 0 and when q and u are equal to 1, the sum r+t isother than 0,  the sum o+r+t+v is less than or equal to 12, and X₁, X₂and X₃, which are identical or different, each represent, independentlyof one another, a hydrogen atom, a halogen atom or an OR₅ radical, inwhich R₅ represents a hydrogen atom or an alkyl radical having from 1 to4 carbon atoms, to form a compound of formula (D),

 in which R′₄ represents either R₄ wherein R₄ represents a divalentradical derived from a chain having from 1 to 10 carbon atoms, in whichchain are optionally inserted one or more structural links chosen fromthe arylene group or the —O—, —S—, —O—C(═O)—, —N(R₆)—C(═O)— or —N(R₆)—fragments, in which fragments R₆ represents a hydrogen atom, analiphatic hydrocarbonaceous radical comprising from 1 to 6 carbon atoms,a benzyl radical or a phenethyl radical, the said chain beingunsubstituted or substituted by one or more radicals chosen from halogenatoms, the hydroxyl group, alkyl radicals comprising from 1 to 4 carbonatoms or the benzyl or phenethyl radicals, or R₄ substituted by aradical originating from the reaction of Z″ with the secondary aminegroup ═N—H, b) the condensation of said compound of formula (D) withsilanol sites of a silica gel, to form the immobilizedpolyazacycloalkane of formula (E):

 in which: X′₂ represents X₂ as defined above or O-(silica gel), and X′₃represents X₃ as defined above or O-(silica gel); c) and the protection,if desired of some of the unreacted silanol sites with Z′, a protectivegroup for the hydroxyl functional group, to form the immobilizedpolyazacycloalkane of formula (E′), corresponding to the formula (E) inwhich all or a portion of the free —OH sites of the silica gel areblocked in the form of OZ′ sites and in particular in the form of(trialykl) silyloxy sites.
 2. The process as defined in claim 1, whereinuse is made, in stage a), of the compound of formula (C₂), correspondingto said formula (C₁) in which: X₁, X₂ and X₃, which are identical ordifferent, each represent, independently of one another, a hydrogenatom, a halogen atom or an OR₅ radical, in which R₅ represents ahydrogen atom or an alkyl radical having from 1 to 4 carbon atoms, Z″represents a bromo radical, an iodo radical or an oxiran-2-yl radical,(X₁), (X₂) and (X₃) each represent an ethoxy radical or a methocyradical, the sum o+r+t+v is less than or equal to 6 and the sum q+u isless than or equal to 1 and in particular of (triethoxy)(3-iodopropyl)-silane, 2-[[[3-(triethoxysilyl)propyl]oxy]methyl]-oxiraneor N-[[4-(bromomethyl)phenyl]methyl]-N-[3-(triethoxysilyl)propyl]amine.3. The process as defined in claim 1, wherein use is made, in stage a),of the compound of formula (A₂), corresponding to formula (A₁) in whichthe R₁ and R₂ radicals each represent a hydrogen atom, and wherein useis in particular made, in stage a), of cyclam or cyclene.
 4. The processas defined in claim 1, in which the compound of formula (D₁),corresponding to the formula (D) as defined above in which at least oneof the R₁, R₂ or R₃ radicals represents a hydrogen atom, is substitutedon one or more of its cyclic nitrogens to form a compound of formula(D′)

in which: R′₄, X₁, X₂ and X₃ are as defined above, R′₁ and R₂, which areidentical or different, represent, independently of one another, ahydrogen atom, a linear or branched alkyl radical having from 1 to 15carbon atoms or a —(CH₂)_(w)—C(═O)—V radical in which V represents oneof the OH, NH₂ or OR₈ radicals in which R₈ represents an alkyl radicalhaving from 1 to 4 carbon atoms, and w represents an integer greaterthan or equal to 1 and less than or equal to 6; W′₁, W′₂ and W′₃, whichare identical or different, represent, independently of one another, adivalent radical chosen from those represented by the general formula(B′): —[(CT₁T₂)_(n)—(N(R′₃)]_(p)—(CT₃T₄)_(m)]_(l)—  (B′)  in which: p,l, n, m, T₁, T₂, T₃ and T₄ have the same meanings as those defined abovefor the formula (B), R′₃ represents, independently of R′₁ or R′₂, ahydrogen atom, a linear or branched alkyl radical having from 1 to 15carbon atoms or a —(CH₂)_(w)—C(═O)—V radical in which V represents oneof the OH, NH₂ or OR₈ radicals, in which R₈ represents an alkyl radicalhaving from 1 to 4 carbon atoms, and w represents an integer greaterthan or equal to 1 and less than or equal to 6, it being understood thatat least one of the R′₁, R′₂ or R′₃ radicals represents a—(CH₂)_(w)—C(═O)—V radical, before being grafted onto the silanol sitesof the silica gel to form an immobilized and functionalized macrocycleof formula (E′), corresponding to the formula (E) in which R₁, R₂ and R₃represent R′₁, R′₂ and R′₃ respectively.
 5. The process as defined inclaim 4, wherein a compound of formula (D′₁) is prepared, which formulacorresponds to the formula (D′) in which none of the R′₁, R′₂ or R′₃radicals represents a hydrogen atom.
 6. The process as defined in claim5, wherein use is made, in stage a), of the compound of formula (A₂) andwherein the preparation is carried out of a compound of formula (D′₂),corresponding to the formula (D′) as defined above in which R′₁, R′₂ andR′₃ each represent a —(CH₂)_(w′)—C(═O)—OR′₈ radical in which w′ is equalto 1, 2 or 3 and R′₈ represents a hydrogen atom, a methyl radical or anethyl radical.
 7. The compound of formula (D), as defined in claim
 1. 8.The compound of formula (D′) as defined in claim
 4. 9. The compoundswith the following names:1-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclododecane,1-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclotridecane,1-[3-(triethoxysilyl)propyl]-1,4,8,11-tetraazacyclotetradecane,1-[3-(triethoxysilyl)propyl]-1,4,8,12-tetraazacyclopentadecane,1-[3-(triethoxysilyl)propyl]-1,5,9,13-tetraazacyclohexadecane,1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,7,10-tetraazacyclododecane,1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,7,10-tetraazacyclotridecane,1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,8,11-tetraazacyclotetradecane,1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,8,12-tetraazacyclopentadecane,1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,5,9,13-tetraazacyclohexadecane,1-[[4-[[[3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,7,10-tetraazacyclododecane,1-[[4-[[[3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,7,10-tetraazacyclotridecane,1-[[4-[[[3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,8,11-tetraazacyclotetradecane,1-[[4-[[[3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,8,12-tetraazacyclopentadecane,1-[[4-[[[3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,5,9,13-tetraazacyclohexadecane,ethyl10-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,ethyl10-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,ethyl11-[3-(triethoxysilyl)propyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,ethyl12-[3-(triethoxysilyl)propyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,ethyl13-[3-(triethoxysilyl)propyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate,ethyl10-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,ethyl10-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,ethyl11-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,ethyl12-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,ethyl13-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate,ethyl10-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,ethyl10-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,ethyl11-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,ethyl12-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,and ethyl13-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,5,9,13-tetraazacyclohexa-decane-1,5,9-propanoate.10. The compound of formula (D₁) as defined in claim
 4. 11. The compoundof formula (D₂) as defined in claim
 6. 12. The compound of formula (D′₁)as defined in claim
 5. 13. The compound of formula (D′₂) as defined inclaim 6.